Influence of allopurinol on thiopurine associated toxicity: A retrospective population-based cohort study.

AIMS: Thiopurines are important for treating inflammatory bowel disease, but are often discontinued due to adverse effects. Concomitant use of allopurinol might lower the risk of these unwanted effects, but large studies in the general population are lacking. The aims of this study were to evaluate rates of hepatotoxicity, myelotoxicity, pancreas toxicity and therapy persistence in adult thiopurine users with or without allopurinol. METHODS: A retrospective population-based cohort study was conducted within current thiopurine users (Clinical Practice Research Datalink). Among these patients, co-use of allopurinol was compared to non-use. Hazard ratios (HRs) for hepatotoxicity, myelotoxicity and pancreatitis were derived using time-dependent Cox proportional hazards models, and were adjusted for potential confounders. Persistence of thiopurine use was evaluated using Log-rank statistics. RESULTS: Patients using thiopurines (n = 37 360) were identified of which 1077 were concomitantly taking allopurinol. A 58% decreased risk of hepatotoxicity was observed in those concomitantly taking allopurinol (HR 0.42; 95% CI 0.30-0.60; NNT 46). Rate of myelotoxicity (HR 0.96; 95% CI 0.89-1.03) was not influenced. Risk of pancreatitis was increased (HR 3.00; 95% CI 1.01-8.93; NNH 337), but was only seen in those with active gout (suggesting confounding by indication). Finally, allopurinol co-users were able to maintain thiopurine therapy over twice as long as those not on allopurinol (3.9 years vs. 1.8 years, P < 0.0001). CONCLUSION: In thiopurine users, allopurinol is associated with a 58% reduced risk of hepatotoxicity. In addition, thiopurine persistence was prolonged by 2.1 years in allopurinol users. These data support the use of allopurinol in individuals requiring thiopurine therapy.

Assessing accuracy of ChatGPT in response to questions from day to day pharmaceutical care in hospitals.

Background: The advent of Large Language Models (LLMs) such as ChatGPT introduces opportunities within the medical field. Nonetheless, use of LLM poses a risk when healthcare practitioners and patients present clinical questions to these programs without a comprehensive understanding of its suitability for clinical contexts. Objective: The objective of this study was to assess ChatGPT's ability to generate appropriate responses to clinical questions that hospital pharmacists could encounter during routine patient care. Methods: Thirty questions from 10 different domains within clinical pharmacy were collected during routine care. Questions were presented to ChatGPT in a standardized format, including patients' age, sex, drug name, dose, and indication. Subsequently, relevant information regarding specific cases were provided, and the prompt was concluded with the query "what would a hospital pharmacist do?". The impact on accuracy was assessed for each domain by modifying personification to "what would you do?", presenting the question in Dutch, and regenerating the primary question. All responses were independently evaluated by two senior hospital pharmacists, focusing on the availability of an advice, accuracy and concordance. Results: In 77% of questions, ChatGPT provided an advice in response to the question. For these responses, accuracy and concordance were determined. Accuracy was correct and complete for 26% of responses, correct but incomplete for 22% of responses, partially correct and partially incorrect for 30% of responses and completely incorrect for 22% of responses. The reproducibility was poor, with merely 10% of responses remaining consistent upon regeneration of the primary question. Conclusions: While concordance of responses was excellent, the accuracy and reproducibility were poor. With the described method, ChatGPT should not be used to address questions encountered by hospital pharmacists during their shifts. However, it is important to acknowledge the limitations of our methodology, including potential biases, which may have influenced the findings.